Increased Type 1 Immune Response in the Bone Marrow Immune Microenvironment of Patients with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation
Abstract Poor graft function (PGF) is a severe complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The question of whether the bone marrow (BM) immune microenvironment is involved in the pathogenesis of PGF remains unresolved. In total, 10 patients with PGF, 30 matched...
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Veröffentlicht in: | Biology of blood and marrow transplantation 2016-08, Vol.22 (8), p.1376-1382 |
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creator | Wang, Yu-Tong Kong, Yuan Song, Yang Han, Wei Zhang, Yuan-Yuan Zhang, Xiao-Hui Chang, Ying-Jun Jiang, Zheng-Fan Huang, Xiao-Jun |
description | Abstract Poor graft function (PGF) is a severe complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The question of whether the bone marrow (BM) immune microenvironment is involved in the pathogenesis of PGF remains unresolved. In total, 10 patients with PGF, 30 matched patients with good graft function after allo-HSCT, and 15 healthy donors were enrolled in this nested case-control study. The Th1, Th2, Tc1, Tc2, and active phenotypes were analyzed by flow cytometry. IFN-γ and IL-4 levels in BM plasma were evaluated using cytometric beads assay. Relative to other subjects, patients with PGF had significantly higher proportions of stimulated CD4+ and CD8+ T cells that produced IFN-γ (Th1 and Tc1 cells) but notably decreased proportions of IL-4-producing T cells (Th2 and Tc2 cells), resulting in a shift of the IFN-γ/IL-4 ratio towards a type 1 response and an elevated percentage of activated CD8+ T cells. Changes in IFN-γ and IL-4 levels in BM plasma were consistent with the cellular results. Our results suggest that dysregulated T cell responses may contribute to the occurrence of PGF after HSCT. |
doi_str_mv | 10.1016/j.bbmt.2016.04.016 |
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The question of whether the bone marrow (BM) immune microenvironment is involved in the pathogenesis of PGF remains unresolved. In total, 10 patients with PGF, 30 matched patients with good graft function after allo-HSCT, and 15 healthy donors were enrolled in this nested case-control study. The Th1, Th2, Tc1, Tc2, and active phenotypes were analyzed by flow cytometry. IFN-γ and IL-4 levels in BM plasma were evaluated using cytometric beads assay. Relative to other subjects, patients with PGF had significantly higher proportions of stimulated CD4+ and CD8+ T cells that produced IFN-γ (Th1 and Tc1 cells) but notably decreased proportions of IL-4-producing T cells (Th2 and Tc2 cells), resulting in a shift of the IFN-γ/IL-4 ratio towards a type 1 response and an elevated percentage of activated CD8+ T cells. Changes in IFN-γ and IL-4 levels in BM plasma were consistent with the cellular results. Our results suggest that dysregulated T cell responses may contribute to the occurrence of PGF after HSCT.</description><identifier>ISSN: 1083-8791</identifier><identifier>EISSN: 1523-6536</identifier><identifier>DOI: 10.1016/j.bbmt.2016.04.016</identifier><identifier>PMID: 27131864</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Allogeneic hematopoietic stem cell transplantation ; Bone Marrow - immunology ; Bone marrow immune microenvironment ; Case-Control Studies ; CD4-CD8 Ratio ; Child ; Child, Preschool ; Female ; Flow Cytometry ; Graft Survival - immunology ; Hematology, Oncology and Palliative Medicine ; Hematopoietic Stem Cell Transplantation ; Humans ; Interferon-gamma - analysis ; Interleukin-4 - analysis ; Male ; Middle Aged ; Poor graft function ; T-Lymphocyte Subsets - immunology ; T-Lymphocytes, Cytotoxic ; Th1 Cells ; Th2 Cells ; Transplantation, Homologous ; Transplants - cytology ; Transplants - immunology ; Type 1 and type 2 immune responses ; Young Adult</subject><ispartof>Biology of blood and marrow transplantation, 2016-08, Vol.22 (8), p.1376-1382</ispartof><rights>American Society for Blood and Marrow Transplantation</rights><rights>2016 American Society for Blood and Marrow Transplantation</rights><rights>Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-7121a845e58664f0710b8b06c5f40c5a226bd954cd6921b2ef3e018edadc01d13</citedby><cites>FETCH-LOGICAL-c455t-7121a845e58664f0710b8b06c5f40c5a226bd954cd6921b2ef3e018edadc01d13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1083879116300350$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27131864$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Yu-Tong</creatorcontrib><creatorcontrib>Kong, Yuan</creatorcontrib><creatorcontrib>Song, Yang</creatorcontrib><creatorcontrib>Han, Wei</creatorcontrib><creatorcontrib>Zhang, Yuan-Yuan</creatorcontrib><creatorcontrib>Zhang, Xiao-Hui</creatorcontrib><creatorcontrib>Chang, Ying-Jun</creatorcontrib><creatorcontrib>Jiang, Zheng-Fan</creatorcontrib><creatorcontrib>Huang, Xiao-Jun</creatorcontrib><title>Increased Type 1 Immune Response in the Bone Marrow Immune Microenvironment of Patients with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation</title><title>Biology of blood and marrow transplantation</title><addtitle>Biol Blood Marrow Transplant</addtitle><description>Abstract Poor graft function (PGF) is a severe complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The question of whether the bone marrow (BM) immune microenvironment is involved in the pathogenesis of PGF remains unresolved. In total, 10 patients with PGF, 30 matched patients with good graft function after allo-HSCT, and 15 healthy donors were enrolled in this nested case-control study. The Th1, Th2, Tc1, Tc2, and active phenotypes were analyzed by flow cytometry. IFN-γ and IL-4 levels in BM plasma were evaluated using cytometric beads assay. Relative to other subjects, patients with PGF had significantly higher proportions of stimulated CD4+ and CD8+ T cells that produced IFN-γ (Th1 and Tc1 cells) but notably decreased proportions of IL-4-producing T cells (Th2 and Tc2 cells), resulting in a shift of the IFN-γ/IL-4 ratio towards a type 1 response and an elevated percentage of activated CD8+ T cells. Changes in IFN-γ and IL-4 levels in BM plasma were consistent with the cellular results. Our results suggest that dysregulated T cell responses may contribute to the occurrence of PGF after HSCT.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Allogeneic hematopoietic stem cell transplantation</subject><subject>Bone Marrow - immunology</subject><subject>Bone marrow immune microenvironment</subject><subject>Case-Control Studies</subject><subject>CD4-CD8 Ratio</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Graft Survival - immunology</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Humans</subject><subject>Interferon-gamma - analysis</subject><subject>Interleukin-4 - analysis</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Poor graft function</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocytes, Cytotoxic</subject><subject>Th1 Cells</subject><subject>Th2 Cells</subject><subject>Transplantation, Homologous</subject><subject>Transplants - cytology</subject><subject>Transplants - immunology</subject><subject>Type 1 and type 2 immune responses</subject><subject>Young Adult</subject><issn>1083-8791</issn><issn>1523-6536</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UsFu1DAQjRCIlsIPcEA-ckkYO3GSlRBSWdF2pVZUdDlbjjOhXmI72E6r_aT-ZR1ty4EDpzdjvTcavzdZ9p5CQYHWn3ZF15lYsFQXUBUJXmTHlLMyr3lZv0w1tGXeNit6lL0JYQcATdWuXmdHrKElbevqOHvYWOVRBuzJdj8hoWRjzGyR_MAwORuQaEviLZKvLj1eSe_d_TPlSivv0N5p76xBG4kbyLWMOpWB3Ot4S66d8-TcyyGSs9mqqJ0lqUFPTsfR_UKLWpELNDK6yWmMqbuJaMgax5FsvbRhGqWNchG-zV4Ncgz47glPsp9n37bri_zy-_lmfXqZq4rzmDeUUdlWHHlb19UADYWu7aBWfKhAcclY3fUrXqm-XjHaMRxKBNpiL3sFtKflSfbxMHfy7s-MIQqjg0oLSYtuDoK2wJOLjJaJyg7U5EMIHgcxeW2k3wsKYolI7MQSkVgiElCJBEn04Wn-3Bns_0qeM0mEzwcCpl_eafQiqOSpwl57VFH0Tv9__pd_5GrUVis5_sY9hp2bvU3-CSoCEyBuliNZbiRJAUoO5SPrQbnT</recordid><startdate>20160801</startdate><enddate>20160801</enddate><creator>Wang, Yu-Tong</creator><creator>Kong, Yuan</creator><creator>Song, Yang</creator><creator>Han, Wei</creator><creator>Zhang, Yuan-Yuan</creator><creator>Zhang, Xiao-Hui</creator><creator>Chang, Ying-Jun</creator><creator>Jiang, Zheng-Fan</creator><creator>Huang, Xiao-Jun</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20160801</creationdate><title>Increased Type 1 Immune Response in the Bone Marrow Immune Microenvironment of Patients with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation</title><author>Wang, Yu-Tong ; Kong, Yuan ; Song, Yang ; Han, Wei ; Zhang, Yuan-Yuan ; Zhang, Xiao-Hui ; Chang, Ying-Jun ; Jiang, Zheng-Fan ; Huang, Xiao-Jun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-7121a845e58664f0710b8b06c5f40c5a226bd954cd6921b2ef3e018edadc01d13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Allogeneic hematopoietic stem cell transplantation</topic><topic>Bone Marrow - immunology</topic><topic>Bone marrow immune microenvironment</topic><topic>Case-Control Studies</topic><topic>CD4-CD8 Ratio</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Graft Survival - immunology</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Humans</topic><topic>Interferon-gamma - analysis</topic><topic>Interleukin-4 - analysis</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Poor graft function</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>T-Lymphocytes, Cytotoxic</topic><topic>Th1 Cells</topic><topic>Th2 Cells</topic><topic>Transplantation, Homologous</topic><topic>Transplants - cytology</topic><topic>Transplants - immunology</topic><topic>Type 1 and type 2 immune responses</topic><topic>Young Adult</topic><toplevel>online_resources</toplevel><creatorcontrib>Wang, Yu-Tong</creatorcontrib><creatorcontrib>Kong, Yuan</creatorcontrib><creatorcontrib>Song, Yang</creatorcontrib><creatorcontrib>Han, Wei</creatorcontrib><creatorcontrib>Zhang, Yuan-Yuan</creatorcontrib><creatorcontrib>Zhang, Xiao-Hui</creatorcontrib><creatorcontrib>Chang, Ying-Jun</creatorcontrib><creatorcontrib>Jiang, Zheng-Fan</creatorcontrib><creatorcontrib>Huang, Xiao-Jun</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biology of blood and marrow transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yu-Tong</au><au>Kong, Yuan</au><au>Song, Yang</au><au>Han, Wei</au><au>Zhang, Yuan-Yuan</au><au>Zhang, Xiao-Hui</au><au>Chang, Ying-Jun</au><au>Jiang, Zheng-Fan</au><au>Huang, Xiao-Jun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased Type 1 Immune Response in the Bone Marrow Immune Microenvironment of Patients with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation</atitle><jtitle>Biology of blood and marrow transplantation</jtitle><addtitle>Biol Blood Marrow Transplant</addtitle><date>2016-08-01</date><risdate>2016</risdate><volume>22</volume><issue>8</issue><spage>1376</spage><epage>1382</epage><pages>1376-1382</pages><issn>1083-8791</issn><eissn>1523-6536</eissn><abstract>Abstract Poor graft function (PGF) is a severe complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The question of whether the bone marrow (BM) immune microenvironment is involved in the pathogenesis of PGF remains unresolved. In total, 10 patients with PGF, 30 matched patients with good graft function after allo-HSCT, and 15 healthy donors were enrolled in this nested case-control study. The Th1, Th2, Tc1, Tc2, and active phenotypes were analyzed by flow cytometry. IFN-γ and IL-4 levels in BM plasma were evaluated using cytometric beads assay. Relative to other subjects, patients with PGF had significantly higher proportions of stimulated CD4+ and CD8+ T cells that produced IFN-γ (Th1 and Tc1 cells) but notably decreased proportions of IL-4-producing T cells (Th2 and Tc2 cells), resulting in a shift of the IFN-γ/IL-4 ratio towards a type 1 response and an elevated percentage of activated CD8+ T cells. Changes in IFN-γ and IL-4 levels in BM plasma were consistent with the cellular results. Our results suggest that dysregulated T cell responses may contribute to the occurrence of PGF after HSCT.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>27131864</pmid><doi>10.1016/j.bbmt.2016.04.016</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adolescent Adult Allogeneic hematopoietic stem cell transplantation Bone Marrow - immunology Bone marrow immune microenvironment Case-Control Studies CD4-CD8 Ratio Child Child, Preschool Female Flow Cytometry Graft Survival - immunology Hematology, Oncology and Palliative Medicine Hematopoietic Stem Cell Transplantation Humans Interferon-gamma - analysis Interleukin-4 - analysis Male Middle Aged Poor graft function T-Lymphocyte Subsets - immunology T-Lymphocytes, Cytotoxic Th1 Cells Th2 Cells Transplantation, Homologous Transplants - cytology Transplants - immunology Type 1 and type 2 immune responses Young Adult |
title | Increased Type 1 Immune Response in the Bone Marrow Immune Microenvironment of Patients with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation |
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